Pre-surgical <sup>68</sup>Ga-PSMA-11 PET for biochemical recurrence risk assessment: A surrogate of pelvic lymph node dissection? Follow-up analysis of a multicenter prospective phase 3 imaging trial.
Authors: Loic Djaileb, Wesley Robert Armstrong, Daniel Thompson, Andrei Gafita, Andrea Farolfi, Tristan Grogan, Matthew R. Cooperberg, Peter Carroll, Samuel L. Washington, Robert Evan Reiter, Matthias Eiber, Ken Herrmann, Wolfgang P. Fendler, Johannes Czernin, Thomas A. Hope, Jeremie Calais
Journal: Journal of Clinical Oncology (2023)

5090 Background: To compare the prognostic value of presurgical PSMA-PET and pelvic lymph nodes invasion (pN1) for biochemical recurrence (BCR) free-survival (FS) in patients with intermediate-risk to high-risk prostate cancer (PCa) treated with radical prostatectomy (RP) and pelvic lymph node dissection. Methods: This is a follow-up study of the surgery cohort included in the multicenter prospective phase 3 imaging trial (n=277; NCT03368547, NCT02611882, NCT02919111). Each 68 Ga-PSMA-11-PET scan was read by three blinded independent readers. Local histopathology risk score (CAPRA-S (Cancer of the Prostate Risk Assessment) score without pN data), PSMA-PET extra-prostatic disease (N1/M1), and pN were used to assess risk of BCR. Patients were followed up after RP by the local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level ≥0.2 ng/ml after RP or an initiation of PCa specific secondary treatment (&gt;6 months after surgery). Univariate, multivariate Cox model, and c-statistic index were performed to assess the prognostic value of PSMA-PET, LNI and its added value to Local histopathology risk score. Results: From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277(87%) patients. Median follow-up from surgery was 32.4 (IQR 23.3-42.9) months. Ninety-one/240 BCR events (38%) were observed. PSMA-PET N1/M1 and pN1 were found in 41/240 (17%) and 67/240 (28%) patients respectively. Local histopathology risk score, PSMA-PET and pN were significant univariate predictors of BCR. Only Local histopathology risk score and PSMA PET were significant in multivariate analysis (HR [95% CI] 1.4 (1.2-1.5) p&lt;0.0001) and (1.7 (1-2.9) p=0.03). Prognostic value of model combining local histopathology and PSMA-PET was not significantly different than model combining local histopathology and pN (c-statistic 0.74 (0.69-0.79) vs 0.73 (0.68-0.78); p= 0.69). In patient group with low-risk Local histopathology score and PSMA-PET N0-M0 only 4/109 (5%) were pN1. In patients with high-risk local histopathology score, a PSMA-PET N1/M1 was associated with a significant lower BCR-FS than a PSMA-PET N0-M0 (median survival (95% CI) 32.7 (14.9-NR) vs 8 (3.2-15.5) p= 0.001). pN1 was found in respectively 25/34 (74%) and 34/90 (38%). Conclusions: Combination of pre-surgical PSMA-PET and Local histopathology was not statistically different than the reference standard, i.e local histopathology and pN to predict BCR-FS. Interestingly rate of discrepancy with pN was low among patient with low histopathology risk and PSMA-PET (N0-M0) and patient with high histopathology risk and PSMA-PET (N1/M1). Clinical trial information: NCT03368547 .